药物性肝损伤患者临床与病理学特征分析*

doi:10.3969/j.issn.1672-5069.2022.04.014

摘要/Abstract

摘要： 目的分析药物性肝损伤(DILI)患者临床和病理学特征及血清细胞因子水平变化,为DILI的早期诊断提供临床依据。方法 2019年5月～2021年5月我院消化内科和肝病科收治的DILI患者60例,行肝活检,停用可疑药物,给予护肝治疗。采用ELISA法检测血清肿瘤坏死因子-ɑ(TNF-ɑ)、白细胞介素-6 (IL-6)、IL-17、IL-10和成纤维细胞生长因子-1(FGF-1)水平。结果本组患者应用抗结核药(23.3%)、中草药(15.0%)、化学药物(11.7%)和保健品(11.7%)是引起DILI常见的药物种类,还有非甾体抗炎药(5.0%)、抗精神类药物(5.0%)、蜂毒(6.7%)、抗生素类(5.0%)、避孕药物(1.7%)、抗癫痫药物(3.3%)、降糖药(6.7%)和减肥药(5.0%);入组时,DILI患者血清ALT、AST和TBIL分别为(198.5±33.1)U/L、(221.7±55.8)U/L和(42.3±12.8)μmol/L,治疗约2 w后,均恢复正常;DILI患者肝组织病理学主要表现为嗜酸性粒细胞(36.7%)、淋巴细胞(18.3%)、中性粒细胞(15.0%)等炎性细胞浸润,其他病理学表现包括浆细胞浸润(10.0%)、脂肪变性(8.3%)、胆汁淤积(5.0%)、肝细胞凋亡(3.3%)和肉芽肿形成(3.3%);入组时,DILI患者血清TNF-ɑ、IL-17、IL-6、IL-10和FGF-1水平分别为(16.5±3.3)pg/ml、(38.8±6.7)pg/ml、(122.9±15.2)pg/ml、(2.0±1.2)pg/ml和(15.3±5.1)pg/ml,治疗后分别为【(2.1±0.8)pg/ml、(15.2±5.4)pg/ml、(45.3±8.4)pg/ml、(5.9±1.4)pg/ml和(26.8±7.6)pg/ml】,差异有统计学意义(P<0.05)。结论了解DILI患者常见的损肝药物、肝功能表现和肝组织病理学特点,及时给予停药和护肝处理,往往预后良好,检测血清细胞因子的变化有助于评估病情。

关键词: 药物性肝损伤, 抗结核药物, 中草药, 肝组织病理学, 细胞因子

Abstract: Objective The aim of this study was to summarize the clinicopathological features and serum cytokine levels in patients with drug-induced liver injury (DILI). Methods 60 patients with DILI were admitted to the Department of Gastroenterology and Hepatology in our hospital between May 2019 and May 2021,and all underwent liver biopsies. The suspected medicines were discontinued and liver function-protecting medicines were given. Serum tumor necrosis factor-ɑ (TNF-ɑ), interleukin-6 (IL-6),IL-17, IL-10 and fibroblast growth factor (FGF-1)levels were detected by ELISA. Results In our series, the drugs suspected for DILI included the anti- tuberculosis medicines accounted in 23.3%, the Chinese herbal medicines in 15.0%, the chemical medicines in 11.7%, the healthcare products in 11.7%, and some other uncommon drugs included non-steroidal anti-inflammatory medicines in 5.0%, antipsychotic drugs in 5.0%, bee venom in 6.7% and antibiotics in 6.7%; at presentation, serum ALT, AST and total bilirubin levels in the 60 patients with DILI were(198.5±33.1)U/L,(221.7±55.8)U/L and (42.3±12.8)μmol/L, all backed to normal at about two week treatment; the liver histopathologic examination showed that the eosinophil (36.7%), lymphocyte (18.3%) and neutrophil (15.0%) infiltration, and other manifestations included plasma cell infiltration (10.0%), steatosis (8.3%), cholestasis (5.0%), apoptosis(3.3%) and granulomatosis(3.3%); at admission, serum TNF-ɑ, IL-17, IL-6, IL-10 and FGF-1 levels were (16.5±3.3)pg/ml, (38.8±6.7)pg/ml, (122.9±15.2)pg/ml, (2.0±1.2)pg/ml and (15.3±5.1)pg/ml, and they changed to [(2.1±0.8)pg/ml, (15.2±5.4)pg/ml, (45.3±8.4)pg/ml, (5.9±1.4)pg/ml and (26.8±7.6)pg/ml, P<0.05] when the disease recovered, significantly different. Conclusion The recognition of common medicines, liver function test and histopathologic changes in patients with DILI will help dealing with them in this circumstance, and discontinue the suspected medicines in time. The prognosis of patients tends to be good.

Key words: Drug-induced liver injury, Pathological features, Anti- tuberculosis medicines, Herbal medicines, Cytokines

刘海涛, 张雷鸣, 李经纬. 药物性肝损伤患者临床与病理学特征分析^*[J]. 实用肝脏病杂志, 2022, 25(4): 508-511.

Liu Haitao, Zhang Leiming, Li Jingwei. Clinical and pathological features in patients with drug-induced liver injury[J]. Journal of Practical Hepatology, 2022, 25(4): 508-511.

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药物性肝损伤患者临床与病理学特征分析^*

Clinical and pathological features in patients with drug-induced liver injury

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